 |
|
|
| |
Kaletra Tablets Once vs Twice Daily
|
| |
| |
Lopinavir Tablets vs Capsules and Once- vs Twice-Daily Dosing
15th Conference on Retroviruses and Opportunistic Infections
February 3-6, 2008
Boston
Mark Mascolini
Lopinavir/ritonavir tablets yielded the same virologic response and similar safety and resistance results when given once versus twice daily, according to 48-week results of the randomized M05-730 trial [1].
The trial randomized 664 antiretroviral-naive people with a viral load above 1000 copies and any CD4 count to one of four regimens (all containing tenofovir/emtricitabine) for 8 weeks:
· Tablets 400/100 mg twice daily
· Capsules 400/100 mg twice daily
· Tablets 800/200 mg once daily
· Capsules 800/200 mg once daily
At week 8 everyone taking capsules once or twice switched to tablets and kept the same dosing frequency. An earlier randomized trial found similar virologic responses with once- and twice-daily capsules but more diarrhea with once-daily dosing [3].
Once- and twice-daily groups in the new study did not differ significantly in gender (78.3% men overall), race (75.2% white), age (average 38.7 years), or pretreatment CD4 count (average 215.5 cells). But the once-daily group had a lower pretreatment viral load than the twice-daily group (4.93 versus 5.05 log copies/mL).
Through 48 weeks 49 people (14.7%) quit the once-daily group and 55 (16.6%) quit the twice-daily group. More people dropped out of the twice-daily arm because of virologic failure (5 [1.5%] versus 2 [0.6%]), nonadherence (9 [2.7%] versus 5 [1.5%], and loss to follow-up (17 [5.1%] versus 10 [3%]). More people quit the once-daily arm because of overall side effects and complications (16 [4.8%] versus 10 [3%]).
A 48-week noncompleter-equals-failure analysis figured that 77% taking lopinavir once daily and 76% taking it twice daily had a viral load below 50 copies. That result established the noninferiority of once-daily dosing to twice-daily dosing. An analysis factoring in the pretreatment between-group difference in viral load did not change that result. Nor did 48-week responses with once- versus twice-daily dosing differ in subgroups starting treatment with a viral load above or below 100,000 copies or a CD4 count above or below 50. None of 10 once-daily patients or 7 twice-daily patients with resistance test results had mutations conferring resistance to lopinavir/ritonavir or tenofovir through 48 weeks. Two in the once-daily arm and 1 in the twice-daily arm had the emtricitabine-related M184V mutation.
Rates of moderate or worse diarrhea, nausea, or vomiting, or grade 3 or 4 lab abnormalities, were similar with once- and twice-daily dosing. People taking lopinavir twice daily had bigger jumps in total cholesterol (+34.5 versus +29 mg/dL), triglycerides (+63.6 versus +44.8 mg/dL), and low-density lipoprotein (LDL) cholesterol (+9.3 versus +5.4 mg/dL) at the end of 48 weeks. HDL cholesterol rose an average 7.2 mg/dL with both once- and twice-daily dosing. The LDL/HDL ratio fell slightly more with once-daily than with twice-daily dosing (-0.43 versus -0.27). The investigators did not report total-to-HDL cholesterol ratio, but it stayed stable in the once-daily group from baseline (3.89, 155.2/39.9] to week 48 (3.91, 184.2/47.1). A ratio under 4.5 is considered good.
At the 8-week point, when everyone switched from capsules to tablets, the capsule and tablet groups did not differ significantly in rates of overall side effects, diarrhea, grade 3 or 4 lab abnormalities, or average change from baseline total cholesterol or triglycerides.
Reference
1. Gathe J, da Silva B, Loutfy M, et al. Study M05-730 primary efficacy results at week 48: phase 3, randomized, open-label study of lopinavir/ritonavir tablets once daily vs twice daily, co-administered with tenofovir DF + emtricitabine in ARV-naive HIV-1-infected subjects. 15th Conference on Retroviruses and Opportunistic Infections. February 3-6, 2008. Boston. Abstract 775.
|
| |
|
|
|
|
|
